In several clinical syndromes studied to date, we have validated our basic original hypothesis that chemosensory dysfunctions are correlated with distinct histological changes in the receptor cells. We have applied our biopsy techniques to human subjects with probable Alzheimer's disease and have defined ultrastructural changes in the olfactory epithelium. The current proposal seeks to extend these studies to include microanalytic evaluation of a crystalline substance found in the olfactory epithelium in probable Alzheimer's disease patients. In addition, we propose to investigate the mitochondrial changes which have been observed in the olfactory epithelial support cells. Evaluation of mitochondrial changes in the olfactory epithelial support cells in a rat model of cytochrome oxidase deficiency is an important corollary to these studies. In addition, the ultrastructural and immunochemical characteristics of a potential nonolfactory chemosensory system will be evaluated: microvillar cells. Studies on the nasal microvillar cells will continue in an attempt to determine whether these cells represent a chemoreceptor population distinct from the classically described olfactory receptor cells. Both immunochemical and tracer techniques will be applied in these studies.